Alcohol is known to interfere with endocrine activities essential to normal sexual function. Impotence, testicular atrophy and gynecomastia have long been associated with chronic alcohol use in men, while menstrual irregularities and their effects on the developing fetus are recognized problems among chronic alcoholic women. Alcohol exerts both acute and long-term effects on the hypothalamic-pituitary-gonadal axis; it blocks testosterone biosynthesis by direct action at the testis, increases testosterone metabolism in the liver, and acts like an opiate in the brain to inhibit luliberin (LHRH) and lutropin (LH) secretion. The proposed studies are aimed at elucidating which neuronal sites(s) and mechanisms(s) are involved in alcohol inhibition of LHRH/LH secretion. We will test the hypothesis that endogenous opioids might mediate this effect, and examine the possible involvement of catecholamines, prostaglandins, and other factors known to regulate LHRH secretion. The principal experimental model is the catheterized rat, from which frequent serial blood samples are collected for periods of several hours on consecutive days. In this paradigm, each rat serves as its own control under relatively unstressed, freely moving conditions, Castrated male rats will be used in most experiments, but pilot studies will be carried out with female rats. In the presence and absence of acutely administered ethanol, LH secretion will be stimulated by agents that act at different levels in the neuronal system that controls LHRH release. Changes in plasma levels of LH, prolactin and ethanol will be measured. A long-range objective is to learn more about neurochemical mechanisms that might be related to the addictive potential of ethanol. Neuropendocrine changes induced by alcohol may serve as measurable correlates of limbic activities important to the behavioral effects of alcohol. The similarity of opiate and alcohol effects on the LHRH/LH endocrine axis is intriguing, but more data must be obtained before speculation about any common mechanisms underlying the actions of these drugs.